Researchers at Johns Hopkins have discovered how our
anti-infection machinery turns itself down and limits the
sniffles, congestion and fevers that are a side effect of
the campaign against invading viruses. The discovery seems
to solve part of the mystery of why the misery of the
common cold lasts only so long.

The key to curbing any excess activity by the immune
system apparently rests with Carabin, a newly discovered
protein made by the specialized white blood cells that
march in when a virus attacks.

Results of a study published online Jan. 17 at
Nature show that Carabin "acts like an internal
brake to dial down the speed and intensity of an immune
response so that it doesn't go too fast or too far, or
careen out of control and attack healthy cells," said
Jun O. Liu, professor of
pharmacology,
neuroscience and
oncology at Johns Hopkins.

Searching for proteins that control immunity, Liu and
his team homed in on those that latch on to parts of cells
that are active during an infection. "Carabin popped out,"
Liu said.

To see what Carabin could do, the research team added
it to white blood cells already primed and ready for
anti-infection action. The more Carabin in the cells, the
less active the cells became.

When people are infected with a cold virus, for
example, the virus enters cells and hijacks the works so
that the cells become viral factories. The immune system's
white blood cells go after these infected cells not only by
fielding chemicals that kill them directly but also by
turning on genes that help out. When Liu and his group
added Carabin to cells and then studied such genes, they
discovered that Carabin disabled the "on" switches, keeping
the genes off.

"By now we were pretty convinced that Carabin can turn
down the immune system, so the next question was, What
controls Carabin?" Liu noted.

Tracking Carabin to its origins, the researchers said
they were surprised to learn that viral infection not only
turns on the immune system machinery but also triggers the
making of Carabin, which in turn shuts off the immune
response.

"It's like having a built-in timer to keep the immune
system in check," Liu said.

If, after further study, Carabin turns out to be a
keystone natural inhibitor of immune responses, Liu added,
it may prove useful in stopping such unwanted immune
reactions as the rejection of transplanted organs.

The research was funded by the Department of
Pharmacology at the Johns Hopkins School of Medicine and
the Keck Foundation.

Authors on the paper are Fan Pan, Luo Sun, David
Kardian, Katharine Whartenby, Drew Pardoll and Liu, all of
Johns Hopkins.